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Abstract
Background. Fine needle aspiration biopsy (FNA) of thyroid nodules under ultrasound control followed by cytological examination is the main method to assess the risk of malignancy of these formations. At the same time, vague and suspicious cytological findings (Bethesda III, IV) are indications for referring patients for surgical treatment, and in some cases this will be excessive. The analysis of molecular markers in the FNA material in addition to cytological examination is a promising way to improve the preoperative diagnosis of thyroid nodules.
Aim. The aim of the study was improving accuracy of preoperative diagnosis of thyroid tumors.
Materials and methods. The validation of the diagnostic capabilities of the domestic molecular genetic test (MGT), developed for the differential diagnosis of thyroid tumors, was carried out on the basis of a retrospective multicenter blind study. The test was based on the assessment of the relative levels of expression of GCM2 and HMGA2 genes, microRNA levels -146b, -221, -375, -31 and -551b, the ratio of mitochondrial and nuclear DNA, as well as the determination of somatic mutation V600E in the BRAF gene. 329 cytological samples were analyzed, which included: 22 (6.7%) with the conclusion of Bethesda II, 226 (68.7%) of Bethesda IV, 6 (1.8%) of Bethesda V, and 75 (22.8%) of Bethesda VI.
Results. The following diagnostic characteristics were obtained for detection of malignant tumors by means of a molecular test in the study: specificity ― 90.8%, sensitivity ― 86.9%, positive predictive value ― 82.3%, negative predictive value ― 93.4%. The overall accuracy was 96.6% for detecting of papillary cancer with the molecular test, 94.4% for follicular cancer, 100% for medullary cancer, and 96.9% for Hürthle cell carcinoma.
Conclusion. The performed study demonstrates the possibility of detecting and typing thyroid tumors with the use of a panel of a small number of molecular markers detected in cytological preparations with real-time PCR. The accuracy of the domestic MGТ is comparable with foreign analogues.
References
Bongiovanni M, Spitale A, Faquin WC et al. The Bethesda System for Reporting Thyroid Cytopathology: a meta-analysis // Acta Cytol. 2012;56(4):333-339. doi:10.1159/000339959
Cibas ES, Ali SZ. The 2017 Bethesda System for Reporting Thyroid Cytopathology // Thyroid. 2017;27:1341–6. doi:10.1089/thy.2017.0500
Cooper DS, Doherty GM, Haugen BR et al. Revised American Thyroid Association management guidelines for patients with thyroid nodules and differentiated thyroid cancer // Thyroid: official journal of the American Thyroid Association. 2009;19(11):1167-214.
Patel KN, Yip L, Lubitz CC et al. The American Association of Endocrine Surgeons Guidelines for the Definitive Surgical Management of Thyroid Disease in Adults // Ann Surg. 2020;271(3):e21-e93. doi:10.1097/SLA.0000000000003580
Nikiforova MN, Mercurio S, Wals A et al. Analytical performance of the ThyroSeq v3 genomic classifier for cancer diagnosis in thyroid nodules // Cancer. 2018;124:1682–1690.
Beaudenon-Huibregtse S, Alexander EK, Guttler RB et al. Centralized molecular testing for oncogenic gene mutations complements the local cytopathologic diagnosis of thyroid nodules // Thyroid. 2014;24:1479–1487.
Patel KN, Angell TE, Babiarz J et al. Performance of a Genomic Sequencing Classifier for the Preoperative Diagnosis of Cytologically Indeterminate Thyroid Nodules // JAMA Surg Published online. 2018. doi:10.1001/jamasurg.2018.1153
Santos MTD, Buzolin AL, Gama RR et al. Molecular Classification of Thyroid Nodules with Indeterminate Cytology: Development and Validation of a Highly Sensitive and Specific New miRNA-Based Classifier Test Using Fine-Needle Aspiration Smear Slides // Thyroid. 2018 Nov 22.
Lupo MA, Walts AE, Sistrunk JW et al. Multiplatform molecular test performance in indeterminate thyroid nodules // DiagnCytopathol. 2020;48(12):1254-1264. doi:10.1002/dc.24564
Haddad RI, Nasr C, Bischoff L et al. NCCN Guidelines Insights: Thyroid Carcinoma, Version 2.2018 // J Natl Compr Canc Netw. 2018;16(12):1429-1440. doi:10.6004/jnccn.2018.0089
Silaghi CA, Lozovanu V, Georgescu CE et al. Thyroseq v3, Afirma GSC, and microRNA Panels Versus Previous Molecular Tests in the Preoperative Diagnosis of Indeterminate Thyroid Nodules: A Systematic Review and Meta-Analysis. Front Endocrinol (Lausanne). 2021;12:649522. Published 13 May 2021. doi:10.3389/fendo.2021.649522
Titov SE, Demenkov PS, Lukyanov SA. et al. Preoperative detection of malignancy in fine-needle aspiration cytology (FNAC) smears with indeterminate cytology (Bethesda III, IV) by a combined molecular classifier // J Clin Pathol. 2020;73(11):722-727. doi:10.1136/jclinpath-2020-206445
Titov SE, Ivanov MK, Demenkov PS et al. Combined quantitation of HMGA2 mRNA, microRNAs, and mitochondrial-DNA content enables the identification and typing of thyroid tumors in fine-needle aspiration smears // BMC Cancer. 2019;19:1010.
Titov SE, Kozorezova ES, Demenkov PS et al. Preoperative Typing of Thyroid and Parathyroid Tumors with a Combined Molecular Classifier // Cancers (Basel). 2021;13(2):237. Published 11 Jan 2021. doi:10.3390/cancers13020237
Mercaldo ND, Lau K.F, Zhou XH. Confidence intervals for predictive values with an emphasis to case-control studies // Stat. Med. 2007;26:2170–2183. doi:10.1002/sim.2677
Reuters KB, Mamone MCOC, Ikejiri ES et al. Bethesda Classification and Cytohistological Correlation of Thyroid Nodules in a Brazilian Thyroid Disease // Center. Eur Thyroid J. 2018;7(3):133-138. doi:10.1159/000488104
Park SY, Hahn SY, Shin JH et al. The Diagnostic Performance of Thyroid US in Each Category of the Bethesda System for Reporting Thyroid Cytopathology // PLoS One. 2016;11(6):e0155898. Published 2016 Jun 27. doi:10.1371/journal.pone.0155898
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